A mathematical model describing methionine metabolism has been tested in an isolated, perfused, rat liver system. The findings are compatible with the hypothesis that the metabolic pathway is a cycle (methionine yields s-adenosylmethionine yields s-adenosylhomocysteine yields homocysteine yields methionine) with a single, irreversible outlet (homocysteine plus serine yields cystathionine). With protein restriction the rate of cycling and the rate of synthesis of cystathionine are decreased - thus conserving methionine. The converse situation occurs when the animals are fed excess amino acid. We have also studied the factors regulating s-adenosylhomocysteine hydrolase in rat liver. The enzyme is increased by hydrocortisone, estradiol and by feeding protein supplements. Measuring enzyme activity in the direction of synthesis of s-adenosylhomocysteine (adenosine plus homocysteine yields adenosylhomocysteine), we found inhibition by both substrates and by s-adenosylmethionine.